Population-based estimate of sibling risk for preterm birth, preterm premature rupture of membranes, placental abruption and pre-eclampsia.

ABSTRACT

BACKGROUND: Adverse pregnancy outcomes, such as preterm birth, preeclampsia and placental abruption, are common, with acute and long-term complications for both the mother and infant. Etiologies underlying such adverse outcomes are not well understood. As maternal and fetal genetic factors may influence these outcomes, we estimated the magnitude of familial aggregation as one index of possible heritable contributions. Using the Missouri Department of Health's maternally-linked birth certificate database, we performed a retrospective population-based cohort study of births (1989-1997), designating an individual born from an affected pregnancy as the proband for each outcome studied. We estimated the increased risk to siblings compared to the population risk, using the sibling risk ratio, lambdas, and sibling-sibling odds ratio (sib-sib OR), for the adverse pregnancy outcomes of preterm birth, preterm premature rupture of membranes (PPROM), placental abruption, and pre-eclampsia. RESULTS: Risk to siblings of an affected individual was elevated above the population prevalence of a given disorder, as indicated by lambdaS (lambdaS (95% CI) 4.3 (4.0-4.6), 8.2 (6.5-9.9), 4.0 (2.6-5.3), and 4.5 (4.4-4.8), for preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively). Risk to siblings of an affected individual was similarly elevated above that of siblings of unaffected individuals, as indicated by the sib-sib OR (sib-sib OR adjusted for known risk factors (95% CI) 4.2 (3.9-4.5), 9.6 (7.6-12.2), 3.8 (2.6-5.5), 8.1 (7.5-8.8) for preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively). CONCLUSION: These results suggest that the adverse pregnancy outcomes of preterm birth, PPROM, placental abruption, and pre-eclampsia aggregate in families, which may be explained in part by genetics.